People With HIV Have Substantially Higher Risk of Sudden Cardiac Death at Low CD4 Counts or Detectable Viral Load

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People living with HIV are 15% more likely to suffer sudden cardiac death compared to people without HIV, according to data presented at the 2019 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, Washington last week.

The study evaluated 3,036 cases of sudden cardiac death among a large cohort of 144,362 U.S. veterans over an average period of 10 years. Subjects in the larger cohort were mostly male (97.2%), African American (47.3%), and were 50 years old on average.

Perhaps unsurprisingly, the risk of sudden cardiac death was even greater among HIV-positive veterans who experienced sustained high viral loads or low CD4 cell counts.

Ultimately, the risk of sudden cardiac death is a "relative risk phenomenon," with risk escalating the longer the virus is unsuppressed, said Matthew Freiberg, M.D., with Vanderbilt University in Nashville, Tennessee. Unfortunately, the study also showed that "just because you remain virally suppressed doesn't mean you never get sudden cardiac death," Freiberg said, speaking at a press conference.

Each year in the United States, an estimated 356,000 people suffer from cardiac arrest outside a hospital, and nearly 90% of these cases are fatal, according to the American Heart Association.

It's well-established that people with HIV have a higher risk of cardiovascular complications. A 2012 study of 2,860 HIV-positive adults in San Francisco found that HIV-positive people had a sudden cardiac death rate 4.5 times higher than could be expected in the local HIV-negative population.

For HIV providers, the new veterans' study presented at CROI reinforces the importance of continuous monitoring for cardiovascular complications -- even among those who have achieved sustained viral suppression.

When evaluating veterans' electronic medical record data, research relied on death certificates to determine whether or not participants had died of sudden cardiac arrest, which had to be listed as the primary cause of death for inclusion in the study. The only exception was when the death certificate listed AIDS as the primary cause of death and sudden cardiac arrest as the secondary cause of death, as the researchers wanted to account for a common practice of listing AIDS as the cause of death even in instances when it shouldn't have been classified as such.

Researchers adjusted for confounding factors, including patient demographics and pre-existing cardiovascular disease, and used Cox proportional hazard regression to determine the link between HIV infection status and the risk of sudden cardiac death.

Ultimately, they concluded that HIV-positive veterans had a 15% higher risk of sudden cardiac death (hazard ratio 1.15, 95% confidence interval [CI] 1.05-1.26). While the researchers didn't evaluate gender differences specifically, Freiberg noted during a CROI press conference that there were about 3,000 women in the study sample and that the rates of sudden cardiac death were about two-fold higher in men than in women.

Researchers also performed a secondary analysis in which they broke down risk factors in various subgroups of HIV-positive individuals according to their viral load or CD4 count.

"We know HIV can be a very heterogeneous disease," said Freiberg. "Depending on the state of the disease, what your viral load looks like, what your CD4 looks like, [that] can dramatically affect risk."

When measured using viral suppression rates, HIV-positive individuals with a viral load less than 500 were at lowest risk (0.98 time-updated adjusted risk, 95% CI 0.87-1.09), and those with a viral load greater than 500 were at much higher risk (1.70 time-updated adjusted risk, 95% CI 1.46-1.98).

The same pattern followed when evaluating risk using CD4 count. HIV-positive individuals with a CD4 count over 500 had the lowest risk of sudden cardiac death (1.03 time-updated adjusted risk, 95% CI 0.90-1.18), followed by those with CD4 count between 500 and 200 (1.11 time-updated adjusted risk, 95% CI 0.97-1.28), then those with a CD4 count less than 200 (1.57 time-updated adjusted risk, 95% CI 1.29-1.92).

The breakdown of risk stratification based on viral load and CD4 count was possible because of the detailed patient history provided in the Veterans Aging Cohort Study, a prospective study of HIV-positive veterans with a massive control group of HIV-negative veterans. Ultimately, about 30% of the overall patients included in the analysis were HIV positive.

Despite the massive size of this study, Freiberg says it's the tip of the iceberg in terms of our understanding of the link between HIV and cardiac risk.

"People with HIV are experiencing the loss of half of their immune system regularly, and what that means in regards to heart attack, stroke, heart failure, and sudden cardiac death, we don't really understand," he said.